Introduction to the Symposium and Studies on the Surfaces of Separated and Synchronized Tumor and Embryonic Cell Populations

Tumor and embryonic cell surfaces are examined in this symposiumwith respect to their roles in cell-cell interactions and inearly development and malignancy. Three sets of studies havebeen recently performed in my laboratory to help elucidate thenature of tumor and embryonic cell surfaces and the means bywhich these cells adhere to each other. We separated an in vivo129/J ascites mouse teratoma into specific subpopuladons ofcells by velocity sedimentation in shallow density gradients.The teratoma consistently separated into two major populations:"large" and "small" cells. Only the large cells displayed "malignant-like"surface characteristics in terms of their agglutinability withcarbohydrate binding lectins. The teratoma cells were also synchronizedin culture with thymidine plus colcemid. In these synchronizedcultures, cellular adhesiveness and glutamine synthetase specificactivity displayed oscillatory patterns with peaks of glutaminesynthetase specific activity occurring just prior to peaks ofadhesivenesss. Also, both glutamine synthetase specific activityand cellular adhesiveness were enhanced by two compounds: actinomycinD and hydrocortisone. Based upon previous work that implicatesL-glutamine in intercellular adhesion, it is not unreasonableto speculate that glutamine synthetase specific activity andcellular adhesiveness may be causally related. The problem ofaltered tumor cell adhesiveness is important because it seems,in part, to be responsible for tumor spread. Finally, the seaurchin embryo system was utilized to identify specific cellsurface carbohydrates that may be involved in intercellularadhesion. In 15 separate experiments with each sugar and with15 different saccharides, D-galactose and N-acetyl-D-galactosaminewere the best inhibitors of rotation-medicated reaggregationof 24-hr sea urchin embryo cells dissociated by removal of divalentcations. ß-galactosidase also inhibited reaggregationof these cells. These results implicate galactopyranosyl-likeresidues in the adhesion of 24-hr sea urchin embryo cells witheach other.     

hw‐quickcheck: an easy‐to‐use computer program for checking genotypes for agreement with Hardy–Weinberg expectations

Deviations from Hardy–Weinberg expectations are frequently a sign of genotyping error. hw‐quickcheck is an easy‐to‐use computer program for detecting departures from Hardy–Weinberg equilibrium. hw‐quickcheck uses exact tests for all of its calculations. These tests include a global test for heterozygote excess/deficiency and genotype‐specific tests.     

Morphological profiling using machine learning reveals emergent subpopulations of interferon-γ–stimulated mesenchymal stromal cells that predict immunosuppression

Background

Although a preponderance of pre-clinical data demonstrates the immunosuppressive potential of mesenchymal stromal cells (MSCs), significant heterogeneity and lack of critical quality attributes (CQAs) based on immunosuppressive capacity likely have contributed to inconsistent clinical outcomes. This heterogeneity exists not only between MSC lots derived from different donors, tissues and manufacturing conditions, but also within a given MSC lot in the form of functional subpopulations. We therefore explored the potential of functionally relevant morphological profiling (FRMP) to identify morphological subpopulations predictive of the immunosuppressive capacity of MSCs derived from multiple donors, manufacturers and passages.

Microsatellite markers developed from Theobroma cacao L. expressed sequence tags

Theobroma cacao L. expressed sequence tags (ESTs) were converted into useful genetic markers for fingerprinting individuals and genetic linkage mapping. Primers were designed to microsatellite‐containing ESTs. Twenty‐two T. cacao accessions, parents of various mapping populations segregating for disease resistance and crop yield characteristics, were tested. Twenty‐seven informative loci were discovered with 26 primer pairs. The number of detected alleles ranged from two to 11 and averaged 4.4 per locus. All 27 markers could be mapped into at least one of the existing F₁ or F₂ populations segregating for agronomically important traits.     

Microsatellites in the striped ground crickets,Allonemobius (Orthoptera: Gryllidae)

Polymorphic di‐, tri‐ and tetranucleotide repeats were examined in Allonemobius to determine whether they could serve as useful markers in studies of sperm precedence, population genetics and hybrid zone structure. Ten microsatellite DNA loci were sufficiently polymorphic to be used for paternity tests and showed no evidence of linkage disequilibrium or deviations from Hardy–Weinberg equilibrium in Allonemobius socius. Nine of 10 of these microsatellites can be amplified from three other Allonemobius species, suggesting that these markers will have widespread utility in this ground cricket genus.     

Delay and failure in treatment seeking after first onset of mental disorders in the World Health Organization's World Mental Health Survey Initiative

Data are presented on patterns of failure and delay in making initial treatment contact after first onset of a mental disorder in 15 countries in the World Health Organization (WHO)''s World Mental Health (WMH) Surveys. Representative face-to-face household surveys were conducted among 76,012 respondents aged 18 and older in Belgium, Colombia, France, Germany, Israel, Italy, Japan, Lebanon, Mexico, the Netherlands, New Zealand, Nigeria, People''s Republic of China (Beijing and Shanghai), Spain, and the United States. The WHO Composite International Diagnostic Interview (CIDI) was used to assess lifetime DSM-IV anxiety, mood, and substance use disorders. Ages of onset for individual disorders and ages of first treatment contact for each disorder were used to calculate the extent of failure and delay in initial help seeking. The proportion of lifetime cases making treatment contact in the year of disorder onset ranged from 0.8 to 36.4% for anxiety disorders, from 6.0 to 52.1% for mood disorders, and from 0.9 to 18.6% for substance use disorders. By 50 years, the proportion of lifetime cases making treatment contact ranged from 15.2 to 95.0% for anxiety disorders, from 7.9 to 98.6% for mood disorders, and from 19.8 to 86.1% for substance use disorders. Median delays among cases eventually making contact ranged from 3.0 to 30.0 years for anxiety disorders, from 1.0 to 14.0 years for mood disorders, and from 6.0 to 18.0 years for substance use disorders. Failure and delays in treatment seeking were generally greater in developing countries, older cohorts, men, and cases with earlier ages of onset. These results show that failure and delays in initial help seeking are pervasive problems worldwide. Interventions to ensure prompt initial treatment contacts are needed to reduce the global burdens and hazards of untreated mental disorders.     

Methane production by microbial mats under low sulphate concentrations

Cyanobacterial mats collected in hypersaline salterns were incubated in a greenhouse under low sulphate concentrations ([]) and examined for their primary productivity and emissions of methane and other major carbon species. Atmospheric greenhouse warming by gases such as carbon dioxide and methane must have been greater during the Archean than today in order to account for a record of moderate to warm palaeoclimates, despite a less luminous early sun. It has been suggested that decreased levels of oxygen and sulphate in Archean oceans could have significantly stimulated microbial methanogenesis relative to present marine rates, with a resultant increase in the relative importance of methane in maintaining the early greenhouse. We maintained modern microbial mats, models of ancient coastal marine communities, in artificial brine mixtures containing both modern [] (c. 70 mm ) and ‘Archean’[] (<0.2 mm ). At low [], primary production in the mats was essentially unaffected, while rates of sulphate reduction decreased by a factor of three, and methane fluxes increased by up to 10‐fold. However, remineralization by methanogenesis still amounted to less than 0.4% of the total carbon released by the mats. The relatively low efficiency of conversion of photosynthate to methane is suggested to reflect the particular geometry and chemical microenvironment of hypersaline cyanobacterial mats. Therefore, such mats were probably relatively weak net sources of methane throughout their 3.5 Ga history, even during periods of low environmental levels oxygen and sulphate.     

Plant chemical defence allocation constrains evolution of local range

Many species of plants in the wild are distributed spatially in patches, the boundaries of which may occur and change because of a complicated interplay between myriad environmental stressors and limitations of, or constraints on, plant coping mechanisms. By examining genetic variation and co‐variation among marker‐inferred inbred lines and sib‐families of an upland wild mustard species within and just a few meters across a natural patch boundary, we show that the evolution of tolerance to the stressful environment outside the patch may be constrained by allocation to glucosinolate compounds (GS) that are defensive against generalist insect herbivores. Several potential stressors were associated with the patch boundary, but carbon isotope ratios indicated that sib‐families with smaller stomatal apertures maintained performance better in response to late season dry conditions, suggesting that drought was an important stressor. The presence of GS may help explain the characteristic patchy distribution of mustards, a relatively diverse and important plant family. This result challenges one end of the continuum of the long‐standing Plant Apparency hypothesis, which essentially states the opposite causation, that low molecular weight toxins like GS are evolutionary responses of patchy distributions and correlated life‐history traits.     

Cladogenesis and endemism in Tanzanian mole‐rats,genus Fukomys: (Rodentia Bathyergidae): a role for tectonics?

African mole‐rats of the family Bathyergidae are subterranean hystricomorph rodents found throughout sub‐Saharan Africa, where the distributional ranges of the most speciose taxa are divided by the African Rift Valley. In particular, mole‐rats of the genera Heliophobius and Fukomys are distributed widely, and their adaptive radiation appears to have been strongly influenced by the geological process of rifting. As a result, virtually all members of the genus Fukomys occur in locations west of the Rift Valley. However, a small number of isolated populations occur east of the Rift Valley in Tanzania, where Heliophobius is widespread and is the predominant bathyergid rodent. Phylogenetic analysis of mitochondrial cytochrome b sequences of previously unstudied Tanzanian mole‐rats (genus Fukomys) and geographically adjacent populations strongly suggests that vicariance in the Western Rift Valley has subdivided populations of mole‐rats and, together with climatic changes, played a role in the isolation of extralimital populations of Fukomys in Tanzania. Together with molecular clock‐based estimates of divergence times, these results offer strong support for the hypothesis that the observed patterns of cladogenesis are consistent with tectonic activity in the ‘Mbeya triple junction’ and Rungwe volcanic province between Lakes Rukwa and Nyasa. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100 , 337–352.